Time for a Worldwide Shift from Oral Polio Vaccine to Inactivated Polio Vaccine Time for a Worldwide Shift from Oral Polio Vaccine to Inactivated Polio Vaccine Aamir Shahzad Max F. Perutz Laboratories, Department of Structural Biology and Biomolecular Chemistry, University of Vienna, Vienna, Austria Reprints or correspondence: Dr Aamir Shahzad, Max F. Perutz Laboratories, Dept of Structural Biology and Biomolecular Chemistry, University of Vienna, Vienna, Austria (aamir.shahzad{at}univie.ac.at). To the Editor—Poliomyelitis (often called polio ) is an acute viral infectious disease caused by poliovirus. Polio was one of the most lethal childhood diseases of the 20th century [ 1 ]. Two polio vaccines are commonly used throughout the world for poliomyelitis. The first was developed by Jonas Salk in 1952; the second was an oral vaccine developed by Albert Sabin.

These 2 vaccines have eradicated polio from most countries and have reduced the worldwide incidence of polio from 350,000 cases in 1988 to just 1300 cases in 2007 [ 1 , 2 ]. The Salk vaccine, or inactivated poliovirus vaccine (IPV), is based on 3 virulent reference strains—Mahoney, MEF-1, and Saukett. The Salk vaccine provides immunoglobulin G-mediated immunity in the bloodstream, which prevents infection from progressing to viremia and protects the neurons. The Salk vaccine is 60%–70% effective against poliovirus 1 and is 90% effective against both poliovirus 2 and 3 [ 1 ]. Oral polio vaccine (OPV) is a live attenuated vaccine: it is produced by passage of poliovirus through nonhuman cells at a subphysiological temperature, which causes spontaneous mutations in the viral genome. OPV is superior to IPV in ease of administration, and there is no need for sterile syringes, as with IPV. OPV also provides longer immunity than does the Salk vaccine.

However, OPV has strict requirements for transport and storage, and this is a big problem in some hot or remote areas [ 2 , 3 ]. Table 1 summarizes the key differences between OPV and IPV. View larger version: Table 1 Comparison of Oral Polio Vaccine (OPV) and Inactivated Poliovirus Vaccine (IPV) A major concern about OPV is its ability to revert to a form that can cause paralysis. Outbreaks of vaccine-associated paralytic poliomyelitis (VAPP) have been reported in many countries of the world [ 2 , 4 ]. In 2005, it was reported that children in a small village in the United States had contracted vaccine-derived polio. In Nigeria, >70 cases have been reported. In 2006, ∼1600 cases of vaccine-induced polio occurred in India, according to the Indian Medical Association Sub-Committee on Immunisation's report on the Polio Eradication Initiative [ 3 ]. The point to be noted is that these cases were reported during repeated mass-immunization campaigns in which repeated doses of OPV were administered.

In 2008, many cases of polio were reported in all provinces of Pakistan, where OPV is used for repeated mass-immunization campaigns. These vaccine-related cases are big challenge for the scientific community if the polio-eradication goal is to be achieved, and there is a need for prompt action to combat the issue [ 1 – 5 ]. According to the World Health Organization, routine immunization with OPV must cease after the eradication of poliovirus because of the danger of outbreaks of circulating vaccine-derived poliovirus and the risk of VAPP. In the regions of the world in which wild-type poliovirus has been eliminated, moving to an IPV or IPV/OPV sequential schedule will reduce or eliminate the risk of VAPP and outbreaks of circulating vaccine-derived poliovirus, as well as increase the likelihood of countries agreeing to stop administering OPV after eradication is achieved. IPV could also be used with OPV in routine schedules to increase immune responses and to decrease the circulation of wild-type poliovirus in countries in which transmission has not been stopped.

IPV alone was very successful in eliminating wild-type poliovirus in many European countries and has been used exclusively in the United States since January 2000. The above observations suggest that OPV has lost its effectiveness in providing herd immunity. It seems that children are getting polio from OPV, and it also seems that OPV is proving to be ineffective in stopping polio transmission from another source. Therefore, the whole world—and especially developing countries—should shift from OPV to IPV, in my opinion. There is still a need for active research in exploring various vaccine strategies for polio and to combat adverse effects associated with polio vaccination; otherwise, the dream of polio eradication will never come true [ 2 – 4 ]. I acknowledge Ms. Gabriele Fieder (University of Vienna) for her kind support. Potential conflicts of interest. A.S.: no conflicts. © 2009 by the Infectious Diseases Society of America Vaccines: VPD-VAC/Polio/main page ShareCompartir One of the Recommended Vaccines by Disease Polio is an infectious disease caused by a virus that lives in the throat and intestinal tract.

It is most often spread through person-to-person contact with the stool of an infected person and may also be spread through oral/nasal secretions. Polio used to be very common in the United States and caused severe illness in thousands of people each year before polio vaccine was introduced in 1955. Most people infected with the polio virus have no symptoms; however, for the less than 1% who develop paralysis it may result in permanent disability and even death. There are two types of vaccine that protect against polio: inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). IPV is given as an injection in the leg or arm, depending on the patient's age. Polio vaccine may be given at the same time as other vaccines. Most people should get polio vaccine when they are children. Children get 4 doses of IPV at these ages: 2 months, 4 months, 6-18 months, and a booster dose at 4-6 years. OPV has not been used in the United States since 2000 but is still used in many parts of the world.

Polio Vaccines HOME >> MEDICINE >> DICTIONARY Polio Vaccines Two polio vaccines are used throughout the world to combat poliomyelitis (or polio). The first was developed by Jonas Salk and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected... Full article >>> '"/> (Date:1/19/2017)... ... 2017 , ... Wells Pharmacy Network announced the completion of ... pharmacy located in Ocala, Florida. , Meeting the Needs of a Growing ... States for high-quality human anti-aging and wellness compounded medications, Wells Pharmacy ... (Date:1/19/2017)... ... January 19, 2017 , ... Remote Medical ... unveiled impressive transportable capabilities with their iMedHD2™ Portable Teleultrasound System. ... RMT technology that delivers HD, dynamic, streaming ultrasound images and video to one ... (Date:1/19/2017)... IL (PRWEB) , ... January 19, 2017 , ... ...

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In this project, we will compare the designs of the experiments and analyze the results. Poliomyelitis , also known as infantile paralysis , is an infectious viral disease that enters through the mouth and is usually spread by contaminated drinking water or food. The virus passes through the stomach and then replicates in the lining of the intestines. Most healthy people infected with virus experience little more than mild fever or diarrhea. In about 1% of infections however, for reasons that are still unclear, the virus spreads to the bloodstream and central nervous system, causing varying degrees of paralysis, and in extreme cases, death. Strangely enough, severe polio tends to be rare in communities with poor hygiene. The reason is that the virus is abundant in such communities, so babies are likely to be exposed to the virus early, while still protected with antibodies from their mothers. Later (assuming that they survive other diseases associated with poor hygiene), these children develop their own antibodies to the virus. The net effect is that in communities with poor hygiene, most people have a natural immunity. History Polio has probably existed throughout human history. For example, there are references to paralytic polio in Egyptian artifacts dating to about 1000 BCE.

However, severe polio was rare in ancient time, because of the hygiene factor discussed above. With improvements in sanitation, the incidence of polio began to rise in the first half of the 20th century, particularly in congested urban areas and particularly in the summer. In the US between 1930 and 1955, polio epidemics seemed to come in waves of ever increasing intensity. The vagaries of polio in terms of time and place, and the haunting images of young children in leg braces and the "iron lung" respirators of the time made polio one of the most feared of all diseases. The following table gives the approximate number of polio cases in the US between 1930 and 1955. The numbers are adapted from Meier [4]. This type of data set is known as a time series 1949 42,000 1. Draw a line graph of the data in the table above. Note the apparent increasing, yet cyclic nature of the data. Franklin Roosevelt contracted polio as a young man in 1921, and was partially paralyzed for the rest of his life.

As president, Roosevelt declared war on polio and thus beginning in the 1930s, considerable effort and resources were directed towards the treatment of polio victims and the search for ways to prevent the disease. In particular, two scientists headed research teams to find a vaccine: Dr. Jonas Salk of the University of Pittsburgh and Dr. Albert Sabin of the University of Cincinnati. Vaccines There are two general method of producing a vaccine for a virus such as polio. Both methods address, in different ways, the fundamental tradeoff between safety and effectiveness. In the method favored by Dr. Salk, the vaccine is prepared from a sample of the virus that is first killed using heat and chemicals (such as formaldehyde). In principle, this method results in a vaccine that is very safe, because naturally, the killed virus in the vaccine is incapable of causing the disease. The vaccine can also be quite effective, if the killed virus is sufficiently intact to cause a strong antibody response in the vaccinated person. Thus, the process of killing the virus can be quite delicate and challenging: . If the process is insufficient, the vaccine will contain live virus and will itself be capable of causing the disease.

If the process is too severe, the proteins of the killed virus will be destroyed to such an extent that the vaccine will be ineffective. In the method favored by Dr. Sabin, the vaccine is prepared from a live, but mutated strain of the virus that is no longer capable of causing severe forms of the disease (such a virus is said to be attenuated ). This method produces a vaccine that is generally very effective, because the live virus replicates in the body, causing a strong antibody response in the vaccinated person. The vaccine can also be quite safe, if the attenuated strain of the virus really is harmless. Again, the development process is delicate and challenging. The difficulty of developing a vaccine that is both safe and effective is illustrated by a polio vaccine developed in the 1930s. This vaccine was abandoned because a number children contracted polio from the vaccine, and several of those died. The 1954 Field Trial By the early 1950s, Salk had finished the development of a killed-virus vaccine, administered in a series of three inoculations. The vaccine was believed to be safe (prematurely, it turned out), but a field trial was needed to judge effectiveness.

Statistical tests of new medical treatments almost always have the same basic format: the responses of a treatment group of subjects who are given the treatment are compared to the responses of a control group of subjects who are not given the treatment. Before we study the designs of the 1954 field trials, let us consider some simple, but flawed designs. 2. Criticize the following design: A sample of children in a specified region are given the vaccine. The rate of polio among these children during a specified period of time is compared to the rate of polio in the same region during the same period of the previous year. 3. Criticize the following design: A sample of children in a specified region are given the vaccine. The rate of polio among these children during a specified period of time is compared to the rate of polio during the same period of time in a different, but similar region. In general, the treatment and control groups must be as similar as possible in every respect except the treatment factor. Thus, because of the vagaries of polio epidemics in time and place, it was essential to have the treatment and control groups drawn from the same regions and the same time periods.

Moreover, a large number of subjects were needed for the trial for the following reasons: The disease is rare. The average incidence during the 1950s was about 50 per 100,000 or 0.0005. Diagnosis is difficult, particularly in mild cases. Mild polio is marked by fever and weakness, which of course, are also symptoms of many other diseases. 4. Suppose that the incidence of polio in a one-year trial period is about 50 per 100,000, and that we want to select a sample large enough so that about 100 persons in the sample would contract polio during the trial period. Assuming perfect diagnoses of the disease, how large should the sample be? The field trial was conducted by the National Foundation for Infantile Paralysis (NFIP). The original design called for vaccination of second-graders at selected schools in selected areas of the country (with the consent of the children's parents, of course). The vaccinated second-graders would form the treatment group. The first and third-graders at the schools would not be given the vaccination, and would form the control group.

This design was known as the observed control experiment . 5. Why do you think the decision was made to have both first and third-graders as the control group, instead of just first-graders or just third-graders? 6. Can you identify any problems with the observed control experiment? Hopefully, your answer to Exercise 6 included two serious issues: selection bias and diagnostic bias . Only those second-graders whose parents consented could be vaccinated, so to a certain extent, the treatment group is self-selecting. The consenting parents tended to have higher incomes than the non-consenting parents. This difference might not matter if the incidence of polio were unrelated to income. But in fact, the incidence of polio tends to be slightly lower among children of poorer parents, because of the hygiene factor discussed earlier. Thus, the selection bias is against the vaccine. Also, parents and doctors attempting to diagnose illnesses would know whether the child had been vaccinated. Such persons, even when trying hard to be objective, tend to be biased in favor of the vaccine--being a bit more likely to diagnose polio in an unvaccinated child and a bit less likely in a vaccinated child.

The net affect of the selection and diagnostic biases is unclear and thus makes the interpretation of the results difficult. A second design was proposed to overcome the deficiencies of the first design. First a sample of children would be selected, all of whose parents consented to vaccination. The sample would be randomly divided into two groups. One group would be given the polio vaccination; the other group would be given a placebo (three injections of inert saltwater that would appear identical to the three injections of the real vaccine). This type of design is known as a randomized control experiment. The randomization tends to nullify all effects (confounding variables) except the treatment effect. Additionally, none of the participants would know the group identity--not the child, not the parents, and not the examining doctors. An experiment of this type, in which both the subjects and the evaluators are ignorant of the treatment/control status, is known as a double-blind experiment. The randomized control, double-blind design is considered the gold standard of statistical designs.

The results of the 1954 field trials are given in the following table, which is adapted from the famous Francis Report [2], the official evaluation of the trials: Experiment 0 Table Notes The False Reports column refers to cases that were initially reported as polio, but were later determined not to be polio. The Not Inoculated row refers to the children in the designated grades who did not participate in the experiment, and includes 8,577 children who received one or two (but not three) injections of placebo. The Incomplete Vaccinations row in both experiments refers to children who received one or two (but not three) injections of the vaccine. The Controls row refers to the total first and third grade populations used as controls in the observed control experiment. 7. Using the results of the randomized controlled experiment, perform an appropriate hypothesis test, at the 0.01 significance level, to see if the incidence of polio is larger for the control group than for the treatment group. State the hypotheses. Compute the polio rate for the control group and for the treatment group. Compute the appropriate test statistic. State your conclusions 8.

Using the results of the observed control experiment, perform an appropriate hypothesis test, at the 0.01 significance level, to see if the incidence of polio is smaller for the treatment group than for the control group. State the hypotheses. Compute the polio rate for the control group and for the treatment group. Compute the appropriate test statistic. State your conclusions 9. Comparing the observed control experiment with the randomized control experiment, do you think that the observed control experiment is biased for or against the vaccine? Postscript After the success of the field trials, the Salk vaccine was put into widespread use. Unfortunately, one improperly manufactured batch of the vaccine caused polio in a number of children, and the vaccination program was temporarily halted (see [4]). By the early 1960s, the Sabin live-strain virus had been perfected and soon replaced the Salk vaccine. Salk was at once lionized by the public and the media and criticized by other scientists, who felt that he had rushed the development of the vaccine for the sake of personal glory (and to beat Sabin).

In an invited review article [1] for the Journal of the American Statistical Association in 1955, shortly after the trials, KA Brownlee did not mince words in his scathing criticism of the original observed control experiment, referring to the design as "stupid and futile," and the results as "worthless." In spite of the problems with the initial design of the statistical experiment, the manufacturing problems, and the excessive media hype, the development of the polio vaccines remains a supreme triumph of the scientific method, a triumph in which statistics played a fundamental role. Because of the vaccines, polio has largely been eradicated in the industrialized world, and countless children and others have been spared untold misery. 1. K. A. Brownlee. "Statistics of the 1954 Polio Vaccine Trials." Journal of the American Statistical Association 50 (1955), 1005-1013. 2. Thomas Francis, Robert Korn, et al. "An Evaluation of the the 1954 Poliomyelitis Vaccine Trials." American Journal of Public Health 45 (1955), 50 page supplement with a 63 page appendix. 3.

David Freedman, Robert Pisani, and Roger Purves. Statistics 3rd edition, WW Norton, 1998. 4. Paul Meier. "Safety of the Poliomyelitis Vaccine." Science 125 (1957) 1067-1071. 5. Paul Meier. "The Biggest Public Health Experiment Ever: The 1954 Field Trial of the Salk Poliomyelitis Vaccine" in Statistics, A Guide to the Unknown , Judith Tanur, Frederick Mosteller, et al. editors, Holden Day, 1978. Web Sites Polio Vaccine: MedlinePlus Drug Information Other names Why get vaccinated? Vaccination can protect people from polio. Polio is a disease caused by a virus. It is spread mainly by person-to-person contact. It can also be spread by consuming food or drinks that are contaminated with the feces of an infected person. Most people infected with polio have no symptoms, and many recover without complications. But sometimes people who get polio develop paralysis (cannot move their arms or legs). Polio can result in permanent disability.

Polio can also cause death, usually by paralyzing the muscles used for breathing. Polio used to be very common in the United States. It paralyzed and killed thousands of people every year before polio vaccine was introduced in 1955. There is no cure for polio infection, but it can be prevented by vaccination. Polio has been eliminated from the United States. But it still occurs in other parts of the world. It would only take one person infected with polio coming from another country to bring the disease back here if we were not protected by vaccination. If the effort to eliminate the disease from the world is successful, some day we won't need polio vaccine. Until then, we need to keep getting our children vaccinated. Who should get polio vaccine and when? Inactivated Polio Vaccine (IPV) can prevent polio. Children: Most people should get IPV when they are children. Doses of IPV are usually given at 2, 4, 6 to 18 months, and 4 to 6 years of age. The schedule might be different for some children (including those traveling to certain countries and those who receive IPV as part of a combination vaccine). Your healthcare provider can give you more information.

Adults: Most adults do not need polio vaccine because they were vaccinated as children. But some adults are at higher risk and should consider polio vaccination including: people traveling to areas of the world, laboratory workers who might handle polio virus, and healthcare workers treating patients who could have polio. These higher-risk adults may need 1 to 3 doses of IPV, depending on how many doses they have had in the past. There are no known risks to getting IPV at the same time as other vaccines. Who should not get IPV or should wait? Tell the person who is giving the vaccine: If the person getting the vaccine has any severe, life-threatening allergies.If you ever had a life-threatening allergic reaction after a dose of IPV, or have a severe allergy to any part of this vaccine, you may be advised not to get vaccinated. Ask your healthcare provider if you want information about vaccine components. If the person getting the vaccine is not feeling well. If you have a mild illness, such as a cold, you can probably get the vaccine today. If you are moderately or severely ill you should probably wait until you recover. Your doctor can advise you. What are the risks from IPV?

As with any medicine, there is a very remote chance of a vaccine causing a serious injury or death. The safety of vaccines is always being monitored. For more information, visit: Other problems that could happen after this vaccine: People sometimes faint after a medical procedure, including vaccination. Sitting or lying down for about 15 minutes can help prevent fainting and injuries caused by a fall. Tell your provider if you feel dizzy, or have vision changes or ringing in the ears. Some people get shoulder pain that can be more severe and longer-lasting than the more routine soreness that can follow injections. This happens very rarely. Any medication can cause a severe allergic reaction. Such reactions from a vaccine are very rare, estimated at about 1 in a million doses, and would happen within a few minutes to a few hours after the vaccination. With any medicine, including vaccines, there is a chance of side effects. These are usually mild and go away on their own, but serious reactions are also possible. Some people who get IPV get a sore spot where the shot was given. IPV has not been known to cause serious problems, and most people don't have any problems at all with it. What if there is a moderate or severe problem?

What should I look for? Look for anything that concerns you, such as signs of a severe allergic reaction, a very high fever, or unusual behavior.Signs of a serious allergic reaction can include hives, swelling of the face or throat, difficulty breathing, a fast heartbeat, dizziness, and weakness. These would start a few minutes to a few hours after the vaccination. What should I do? If you think it is a severe allergic reaction or other emergency that can't wait, call 9-1-1 or get to the nearest hospital. Otherwise, call your clinic.Afterward, the reaction should be reported to the Vaccine Adverse Event Reporting System (VAERS). Your doctor should file this report, or you can do it yourself through the VAERS web site at or by calling 1-800-822-7967. VAERS does not provide medical advice. The National Vaccine Injury Compensation Program The National Vaccine Injury Compensation Program (VICP) is a federal program that was created to compensate people who may have been injured by certain vaccines.

Persons who believe they may have been injured by a vaccine can learn about the program and about filing a claim by calling 1-800-338-2382 or visiting the VICP website at . There is a time limit to file a claim for compensation. How can I learn more? Ask your healthcare provider. He or she can give you the vaccine package insert or suggest other sources of information. Call your local or state health department. Contact the Centers for Disease Control and Prevention (CDC): call 1-800-232-4636 ( 1-800-CDC-INFO ) or visit CDC's website at Polio Vaccine Information Statement. U.S. Department of Health and Human Services/Centers for Disease Control and Prevention National Immunization Program. 7/20/2016. Polio_vaccine Polio_vaccine Polio vaccine Two polio vaccines are used throughout the world to combat polio. The first was developed by Jonas Salk , first tested in 1952, and announced to the world by Salk on April 12, 1955. It consists of an injected dose of inactivated (dead) poliovirus.

The second was an oral vaccine developed by Albert Sabin using attenuated poliovirus. Human trials of Sabin's vaccine began in 1957 and it was licensed in 1962. [1] The two vaccines have eradicated polio from most of the countries in the world [2] [3] and reduced the worldwide incidence from an estimated 350,000 cases in 1988 to fewer than 2000 cases in 2006. [4] [5] Contents 7 References The "great race" In 1936 Maurice Brodie, a research assistant at New York University, attempted to produce a formaldehyde -killed polio vaccine from ground-up monkey spinal cords. His initial attempts were hampered by the difficulty of obtaining enough virus. Brodie first tested the vaccine on himself and several of his assistants. He then gave the vaccine to three thousand children: many developed allergic reactions, but none developed immunity to polio. [6] Philadelphia pathologist John Kollmer also claimed to have developed a vaccine that same year, but it too produced no immunity and was blamed for causing a number of cases, some of them fatal.

[7] A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized for their labors with a Nobel Prize in Physiology or Medicine in 1954. [8] Other important advancements that lead to the development of polio vaccines were: the identification of three poliovirus serotypes (Poliovirus type 1 (PV1 or Mahoney), PV2 (Lansing), and PV3 (Leon)), the finding that preceding paralysis, the virus must be present in the blood, and the demonstration that administration of antibodies in the form of gamma-globulin protects against paralytic polio. [5] [9] In 1952 and 1953 the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, up from a typical number of around 20,000 cases a year.

Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox. Polish-born virologist and immunologist Hilary Koprowski , who also worked at Lederle, claims to have created the first successful polio vaccine (in 1950) but his vaccine, a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salk's polio vaccine (a dead inject-able vaccine) reached the market. The samples of difficult-to-manufacture attenuated virus Albert Sabin used to develop his oral polio vaccine were given to him by Hilary Koprowski. "Koprowski would later complain that the polio vaccine he had discovered became known as the Sabin vaccine." [10] Koprowski's own vaccine was ultimately tested, but the outcome was a failure. After the attenuated live virus entered the body, it sometimes reverted to a virulent state.

[11] Nevertheless, from 1957 to 1960, large scale tests were carried out in the Congo. The results have been controversial [12] , and accusations in the 1990s arose that the vaccine created the conditions necessary for the transmission of SIV from chimpanzees to humans, causing HIV/AIDS. The development of two polio vaccines lead to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States were in 1979, when an outbreak occurred among the Amish in several Midwest states. [13] The disease was entirely eradicated in the Americas by 1994. [14] Salk's "inactivated polio vaccine" The first effective polio vaccine was developed in 1952 by Jonas Salk at the University of Pittsburgh.

The Salk vaccine, or inactivated poliovirus vaccine (IPV), is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. [5] The injected Salk vaccine confers IgG -mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome. However, because it offers no protection to the mucosal lining of the intestine, people vaccinated with Salk's vaccine can still carry the disease and spread it to unvaccinated individuals. Salk's vaccine was licensed in 1955, and immediately children's vaccination campaigns were launched. In 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania. Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis; the largest medical experiment in history.

The test began with some 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and would eventually involve 1.8 million children, in 44 states from Maine to California. [15] By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo , consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio. [10] The results of the field trial were announced April 12, 1955 (the tenth anniversary of the death of Franklin Roosevelt). The Salk vaccine had been 60 - 70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. [16] In the U.S, following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell to 5,600 by 1957.

[17] The IPV vaccine was used extensively in the U.S. until the early 1960s. An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice in the United States. [13] Sabin's "oral polio vaccine" Eight years after Salk's success, Albert Sabin developed the oral polio vaccine (OPV). [18] The OPV is a live-attenuated vaccine, produced by the passage of the virus through non-human cells at a sub-physiological temperature, which produces spontaneous mutations in the viral genome. There are 57 nucleotide substitutions which distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. [5] The primary attenuating factor common to all three Sabin vaccines is a mutation located in the virus's internal ribosome entry site (or IRES ) [19] which alters stem-loop structures, and reduces the ability of poliovirus to translate its RNA template within the host cell.

[20] The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. The OPV proved to be superior in administration, and also provided longer lasting immunity than the Salk vaccine. [19] Although Salk's vaccine had reduced the incidence of polio to a tiny fraction of what it was in the early 1950s, it was the oral live-virus vaccine that enabled the complete elimination of the wild polio virus in the United States. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. [6] A second wave of mass immunizations lead to a further dramatic decline in the number of polio cases. In 1961, only 161 cases were recorded in the United States.

[21] Iatrogenic (vaccine-induced) polio A major concern attributable to the oral polio vaccine (OPV) is that it can revert to a virulent form. [22] Clinical disease caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. [23] This is believed to be a rare event, but outbreaks of vaccine-derived poliovirus (VDPV) have been reported, and tend to occur in areas of low coverage by OPV, presumably because the OPV is itself protective against the related outbreak strain. [24] [25] Reversion is not possible in IPV vaccinations used in the U.S., and thus vaccine-induced polio is not a concern. The rate of vaccine-associated paralytic poliomyelitis (VAPP) varies by region but is generally about 1 case per 750,000 vaccine recipients. [26] VAPP is more likely to occur in adults than in children.

In immunodeficient children, the risk of VAPP is almost 7,000 times higher, particularly for persons with B-lymphocyte disorders (e.g., agammaglobulinemia and hypogammaglobulinemia), which reduce the synthesis of protective antibodies. [23] The World Health Organisation considers the benefits of vaccination to far outweigh the risk of vaccine derived polio. Outbreaks of vaccine derived polio have been stopped by multiple rounds of high-quality vaccination, in order to immunise the entire population. [27] Outbreaks of VAPP occurred independently in Belarus (1965–66), Egypt (1983–1993), Hispaniola (2000–2001), Philippines (2001), Madagascar (2001–2002), [28] and in Haiti (2002), where political strife and poverty have interfered with vaccination efforts. [29] In 2006 an outbreak of vaccine-derived poliovirus occurred in China.

[30] Cases have been reported from Cambodia (2005-2006), Myanmar (2006-2007), Iran (1995, 2005-2007), Syria, Kuwait and Egypt, while in northern Nigeria, 69 cases were reported in 2007. [31] Vaccination schedule Following the widespread use of poliovirus vaccine in the mid-1950s, the incidence of poliomyelitis declined rapidly in many industrialized countries. As the incidence of wild polio diminishes, nations transition from use of the oral vaccine back to the injected vaccine because the risk of latrogenic polio outweighs the risk of subclinical transmission. The use of OPV was discontinued in the United States in 2000, but it continues to be used around the globe. [13] In 2002, a pentavalent (5-component) combination vaccine (called Pediarix) containing IPV was approved for use in the United States.

The vaccine also contains combined diphtheria, tetanus, and acellular pertussis vaccines ( DTaP ) and a pediatric dose of hepatitis B vaccine. [13] In the UK the change from OPV to IPV occurred in 2004 and for convenience polio vaccine was combined with tetanus, diphtheria, pertussis and Haemophilus influenzae type b vaccines. [32] The first dose of polio vaccine is given shortly after birth, usually between 1-2 months of age, a second dose is given at 4 months of age. [13] The timing of the third dose depends on the vaccine formulation but should be given between 6–18 months of age. [32] Booster vaccination are given at 4 to 6 years of age, for a total of four doses at or before school entry. [33] In some countries a fifth vaccination is given during adolescence. [32] Routine vaccination of adults (18 years of age and older) in developed countries is neither necessary nor recommended because most adults are already immune and have a very small risk of exposure to wild poliovirus in their home countries.

[13] Efficacy In the generic sense, vaccination works by priming the immune system with an 'immunogen'. Stimulating immune response, via use of an infectious agent, is known as immunization. Vaccine efficacy is defined by the amount of immunity against infection a particular vaccine provides, and is often measured by detection of protective antibodies in the blood. [34] The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community. [35] Because there is no long term carrier state for poliovirus in immunocompetent individuals, polioviruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of times appears to be remote, interruption of person-to person transmission of the virus by vaccination is the critical step in global polio eradication. [35] After two doses of inactivated polio vaccine (IPV), ninety percent or more of individuals develop protective antibody to all three serotypes of poliovirus, and at least 99% are immune to poliovirus following three doses.

A single dose of oral polio vaccince produces immunity to all three poliovirus serotypes in approximately 50% of recipients. [13] Three doses of live-attenuated OPV produce protective antibody to all three poliovirus types in more than 95% of recipients. OPV produces excellent immunity in the intestine, the primary site of wild poliovirus entry, which helps prevent infection with wild virus in areas where the virus is endemic. [33] IPV produces less gastrointestinal immunity than does OPV, so persons who receive IPV are more easily infected with wild poliovirus. In regions without wild poliovirus, inactivated polio vaccine is the vaccine of choice. [33] In regions with higher incidence of polio, and thus a different relative risk between efficacy and reversion of the vaccine to a virulent form, live vaccine is still used. The live virus also has stringent requirements for transport and storage, which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is probably lifelong. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to provide protection for many years.

[36] Contamination concerns In 1960, it was determined that the rhesus monkey kidney cells used to prepare the poliovirus vaccines were infected with a virus called SV40 (or Simian Virus-40). [37] SV40, also discovered in 1960, is a naturally occurring virus that infects monkeys. In 1961, SV40 was found to cause tumors in rodents. [38] More recently, the virus was found in certain forms of cancer in humans, for instance brain and bone tumors, mesotheliomas , and some types of non-Hodgkin's lymphoma. [39] [40] However, it has not been determined that SV40 causes these cancers. [41] SV40 was found to be present in stocks of the injected form of the polio vaccine (IPV) in use between 1954 to 1962, it is not found in the OPV form (which was licensed later).

Over 98 million Americans received one or more doses of polio vaccine between 1955 to 1963 when a proportion of vaccine was contaminated with SV40; it has been estimated that 10 - 30 million Americans may have received a dose of vaccine contaminated with SV40. [37] Later analysis suggested that vaccines produced by the former Soviet bloc countries until 1980, and used in the USSR, China, Japan, and several African countries, may have been contaminated; meaning hundreds of millions more may have been exposed to SV40. [42] In 1998, the National Cancer Institute undertook a large study, using cancer case information from the Institutes SEER database. The published findings from the study revealed that there was no increased incidence of cancer in persons who may have received vaccine containing SV40. [43] Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not.

[44] The question of whether SV40 causes cancer in humans remains controversial however, and the development of improved assays for detection of SV40 in human tissues, will be needed to resolve the controversy. [41] See also The mathematics of mass vaccination Herd immunity ^ A Science Odyssey: People and Discoveries. PBS (1998). Retrieved on 2007-08-14. ^ Aylward R (2006). "Eradicating polio: today's challenges and tomorrow's legacy". Ann Trop Med Parasitol 100 (5-6): 401-13. PMID 16899145. ^ Schonberger L, Kaplan J, Kim-Farley R, Moore M, Eddins D, Hatch M (1984). "Control of paralytic poliomyelitis in the United States". Rev. Infect. Dis. 6 Suppl 2: S424-6. PMID 6740085. ^ CDC Global Health - Polio - What Is Polio?

ShareCompartir Two types of vaccine protect against polio: oral poliovirus vaccine (OPV) and inactivated poliovirus vaccine (IPV) (given as an injection in the leg or arm, depending on the patient's age). Polio, or poliomyelitis, is a crippling and potentially deadly infectious disease. It is caused by the poliovirus. The virus spreads from person to person and can invade an infected person’s brain and spinal cord, causing paralysis (can’t move parts of the body). Symptoms Most people who get infected with poliovirus (about 72 out of 100) will not have any visible symptoms. About 1 out of 4 people with poliovirus infection will have flu-like symptoms that may include— Sore throat Stomach pain These symptoms usually last 2 to 5 days then go away on their own.

A smaller proportion of people with poliovirus infection will develop other more serious symptoms that affect the brain and spinal cord: Paresthesia (feeling of pins and needles in the legs) Meningitis (infection of the covering of the spinal cord and/or brain) occurs in about 1 out of 25 people with poliovirus infection Paralysis (can’t move parts of the body) or weakness in the arms, legs, or both, occurs in about 1 out of 200 people with poliovirus infection Paralysis is the most severe symptom associated with polio because it can lead to permanent disability and death. Between 2 and 10 out of 100 people who have paralysis from poliovirus infection die because the virus affects the muscles that help them breathe. Even children who seem to fully recover can develop new muscle pain, weakness, or paralysis as adults, 15 to 40 years later. This is called post-polio syndrome . Note that "poliomyelitis" (or "polio" for short) is defined as the paralytic disease. So only people with the paralytic infection are considered to have the disease. Transmission Poliovirus only infects humans.

It is very contagious and spreads through person-to-person contact. The virus lives in an infected person’s throat and intestines. It enters the body through the mouth and spreads through contact with the feces (poop) of an infected person and, though less common, through droplets from a sneeze or cough. You can get infected with poliovirus if you have feces on your hands and you touch your mouth. Also, you can get infected if you put in your mouth objects like toys that are contaminated with feces (poop). An infected person may spread the virus to others immediately before and about 1 to 2 weeks after symptoms appear. The virus can live in an infected person’s feces for many weeks. It can contaminate food and water in unsanitary conditions. People who don’t have symptoms can still pass the virus to others and make them sick. Prevention Polio vaccine protects children by preparing their bodies to fight the polio virus. Almost all children (99 children out of 100) who get all the recommended doses of vaccine will be protected from polio.

There are two types of vaccine that can prevent polio: inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV). Only IPV has been used in the United States since 2000; OPV is still used throughout much of the world. More About Polio Page last reviewed: October 3, 2014 Page last updated: October 15, 2014 Content source: Centers for Disease Control and Prevention 1600 Clifton Road Atlanta, GA 30329-4027 USA 800-CDC-INFO (800-232-4636) Polio Vaccine: "Unconditional Surrender" 1956 Eli Lilly Development of the Salk Vaccine - YouTube Polio Vaccine: "Unconditional Surrender" 1956 Eli Lilly Development of the Salk Vaccine Want to watch this again later? Sign in to add this video to a playlist. Need to report the video? Sign in to report inappropriate content. The interactive transcript could not be loaded. Loading... Rating is available when the video has been rented. This feature is not available right now. Please try again later.

Published on Nov 1, 2012 more at "The development of polio vaccine and the significance of its discovery." Public domain film from the Library of Congress Prelinger Archive, slightly cropped to remove uneven edges, with the aspect ratio corrected, and mild video noise reduction applied. The soundtrack was also processed with volume normalization, noise reduction, clipping reduction, and/or equalization (the resulting sound, though not perfect, is far less noisy than the original). Poliomyelitis (pōlee-ō-mī-ə-lītiss), often called polio or infantile paralysis, is an acute, viral, infectious disease spread from person to person, primarily via the fecal-oral route. The term derives from the Greek poliós (πολιός), meaning "grey", myelós (µυελός "marrow"), referring to the grey matter of the spinal cord, and the suffix -itis, which denotes inflammation., i.e., inflammation of the spinal cord's grey matter, although a severe infection can extend into the brainstem and even higher structures, resulting in polioencephalitis, producing apnea that requires mechanical assistance such as an iron lung...

Two polio vaccines are used throughout the world to combat poliomyelitis (or polio). The first was developed by Jonas Salk and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated (dead) poliovirus. An oral vaccine was developed by Albert Sabin using attenuated poliovirus. Human trials of Sabin's vaccine began in 1957 and it was licensed in 1962. Because there is no long term carrier state for poliovirus in immunocompetent individuals, polioviruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote. Therefore, interruption of person to person transmission of the virus by vaccination is the critical step in global polio eradication. The two vaccines have eliminated polio from most countries in the world, and reduced the worldwide incidence from an estimated 350,000 cases in 1988 to 1,652 cases in 2007...

A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948 Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that there were a few unused tubes. He retrieved a sample of mouse brain infected with polio virus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow but the polio cultures were successful. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio... The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest states.

A global effort to eradicate polio, led by the World Health Organization, UNICEF, and The Rotary Foundation, began in 1988 and has relied largely on the oral polio vaccine developed by Albert Sabin. The disease was entirely eradicated in the Americas by 1994. Polio was officially eradicated in 36 Western Pacific countries, including China and Australia in 2000. Europe was declared polio-free in 2002. As of 2008, polio remains endemic in only four countries: Nigeria, India, Pakistan, and Afghanistan. Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occurs, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained... Category

Question: The Salk vaccine is one of two vaccines used throughout the world to combat what disease?
Answer: poliomyelitis